Dichloromethane → (R)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate

HRID 2099812Notes

Reaction equation

HRID 2099812 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](/[CH:9]=[C:10](\[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])/[C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=1[CH3:25].C(Cl)Cl>[B-](F)(F)(F)F.CC[C@H]1P(C2C(P3[C@H](CC)CC[C@H]3CC)=CC=CC=2)[C@H](CC)CC1.C1[CH][CH]CC[CH][CH]C1.[Rh].CO>[NH2:1][C:2]1[C:3]([CH3:25])=[CH:4][C:5]([CH2:9][C@@H:10]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C:11]([O:13][CH3:14])=[O:12])=[CH:6][C:7]=1[CH3:8]

Participants

5

Reactant 2

HCID 6344DichloromethaneHCID 66605272(Z)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate

Product 1

HCID 86605338(R)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate

Reagents, catalysts & solvents 2

HCID 11549211CID 11549211CatalystHCID 887MethanolSolvent

Procedure

(Z)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate (84.5 g, 239 mmol) was weighed into a flame-dried 2 L Parr shaker, followed by the addition of methylene chloride (300 mL) and methanol (300 mL). The bottle was swirled to form a light brown suspension, and this suspension was degassed by a flow of nitrogen for 30 min. Following addition of (−)-1,2-bis((2R,5R)-2,5-diethylphospholano)bezene(cyclooctadiene)rhodium(I)tetrafluoroborate ([(2R,5R)-Et-DuPhosRh]BF4) (2.11 g, 3.20 mmol), the bottle was put onto a Parr Hydrogenator. After 5 cycles of purging with hydrogen (60 psi) and vacuum, the final hydrogen pressure was set at 65 psi and the suspension was agitated at room temperature for 16 h (after 3 h, the suspension became a clear solution), and the reaction was complete. Solvents were removed and the residue was subjected to flash chromatography on silica gel using ethyl acetate/methylene chloride (1:9) as the eluent to afford the title compound as a very light tan solid (82.9 g, 98% yield). 1H-NMR (DMSO-d6) δ 7.70 (d, J=7.9 Hz, 1H), 7.37-7.28 (m, 5H), 6.68 (s, 2H), 5.00 (s, 2H), 4.41 (s, 2H), 4.15-4.10 (m, 1H), 3.62 (s, 3H), 2.82 (dd, J=13.7, 5.2 Hz, 1H), 2.65 (dd, J=13.4, 9.8 Hz, 1H), 2.04 (s, 6H); 3C-NMR (DMSO-d6) δ 172.5, 155.9, 142.6, 136.9, 128.3, 128.2, 127.7, 127.5, 124.0, 120.4, 65.3, 56.1, 51.7, 35.9, 17.7.

Workup

  1. customto form a light brown suspension
  2. customthis suspension was degassed by a flow of nitrogen for 30 min
  3. customAfter 5 cycles of purging with hydrogen (60 psi) and vacuum
  4. customSolvents were removed

Sources & evidence

ORD record
ord-d0decdc8f4d9458da7785a3cf191728f
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

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